Studies on treatment of chronic hepatitis B, C and D

Tsji Pa, physician to the Chinese emperor Hoang Ti (2674-2575 B.C.), described the syndrome of jaundice with fatigue, arthralgia and malaise as related to diseases of the liver. At that t"1me the treatment varied from administering herbs to restoring the yinyang balance with acupuncture (1 }. Two thousand years later Hippocrates described the same syndrome and differentiated liver disease due to the abuse of wine, a fulminant form of hepatitis and a third form that rendered the patient immune after recovery. His therapy consisted of melikraton (made from honey) and venapuncture (2). In the same era liver disease in India was treated with herbs among which Phyllanthus amarus; this plant contains alkaloids, galactosamines and flavonoids, which are substances that have an antihepatotoxic and possibly an antiviral activity (3.4,5). In the previous century jaundice was described to a gastroduodenitis with a catarrhal obstruction to bile (Bamberger 1855, Virchow 1865). The first report of a parenteraUy transmitted outbreak of hepatitis appeared by the end of the 19th century in factory personnel after revaccination against smallpox (LUrman 1885). In 1937 epidemiologic data accumulated to substantiate the existence of an infectious form of hepatitis, with outbreaks in schools, hospitals and other institutions (Sergeant 1937, Lisney 1937, Barber 1937, Cullinan 1939). Until the sixties, the main treatment for hepatitis remained symptomatic with rest, a diet rich in carbohydrates, low in fat and free of alcohol combined with laxatives and ample fluid. For the prevention of liver dystrophy a bovine adrenal extract was advised (6). WaldenstrOm (1950) described a serious form of chronic hepatitis in young women with liver cirr'hosis, plasma cell infiltration of the liver and hypergammaglobulinemia. This disease was associated with high morbidity and mortality, and because of hypergammag!obulinemia and plasmacell infiltration in the liver, immunosuppressive therapy with prednisone seemed obvious (7}. The hypothesis of immunologic damage to the liver led to controlled, clinical studies evaluating the effect of immunosuppressive therapy. Treament with prednisone improved liver function and life expectancy in patients compared to untreated control patients (8,9, 1 0). The etiology of this immunologically induced hepatitis was unknown.aims of the study Hepatitis 8: Hepatitis C: Hepatitis 0: -evaluating the effect of acyclovir, zidovudine and Phyllanthus amarus on HBV replication in order to improve current treatment regimes concerning H Be-seroconversi on -defining quantitative HBeAg and HBV DNA analysis as parameters to monitor antiviral treatment - investigating the influence of indomethacin and paracetamol on the antiviral effect of a-IFN -evaluating the effect of rifampicin in addition to a-IFN treatment in a partial responder to a-IFN therapy - documenting that chronic hepatitis C complicated by coinfection with HIV can mimic autoimmune type chronic hepatitis and that antiviral therapy can lead to sustained remission of of hepatitis C. -evaluating the effect of treatment with a-IFN and ACV on chronic hepatitis

Does effective diastolic coronary venous retroperfusion depend on arterial-like blood pressure in the coronary sinus

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Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

No advantage of quadruple- or triple-class antiretroviral therapy as initial treatment in patients with very high viraemia

We assessed whether quadruple or triple-class therapy for the initial treatment of HIV-1 infection provides a virological benefit over standard triple therapy in patients with very high plasma viraemia. The assessment was made based on a national observational HIV cohort in the Netherlands. Inclusion criteria were age ≥18 years, treatment-naive, plasma viral load (pVL) ≥500,000 copies/ml and initiation of quadruple or triple therapy between 2001 and 2011. Time to viral suppression, defined as pVL <50 copies/ml, was compared between the two groups using Kaplan-Meier plots and multivariate Cox regression analysis. A total of 675 patients were included: 125 (19%) initiated quadruple and 550 (81%) triple therapy. Median pVL was 5.9 (IQR 5.8-6.1) log(10) copies/ml in both groups (P=0.49). 22 (18%) patients on quadruple and 63 (12%) on triple therapy interrupted the treatment regimen because of drug-related toxicity (P=0.06). Median time to viral suppression was 5.8 (IQR 4.6-7.9) and 6.0 (4.0-9.4) months in the patients on quadruple and triple therapy, respectively (log-rank, P=0.42). In the adjusted Cox analysis, quadruple therapy was not associated with time to viral suppression (HR 1.07 [95% CI 0.86, 1.33], P=0.53). Similar results were seen when comparing triple- versus dual-class therapy (n=72 versus n=601, respectively). Initial quadruple- or triple-class therapy was equally effective as standard triple therapy in the suppression of HIV-1 in treatment-naive patients with very high viraemia and did not result in faster pVL decreases, but did expose patients to additional toxicit

Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering socio-demographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0-52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63-15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04-12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02-6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27-192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39-8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19-2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60-14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MS